Serum drug levels of an antiepileptic drug should be monitored when certain conditions are present. Indiscriminate use of blood level determination should be avoided.
Routine determination (based on theoretical grounds):
(1) after initiation of therapy
(1a) after starting therapy
(1b) usually several weeks later, to confirm first value
(2) once or twice a year to confirm compliance
(3) after each change in the drug regimen:
(3a) change in dosage
(3b) change of antiepileptic regimen
(3c) change in other medications
Tailored determinations for a specific purpose:
(4) When a patient:
(4a) complains of toxic signs, possibly dosage-related
(4b) is insidiously deteriorating, and it is not clear whether the condition is disease or drug-related.
(5) To check for compliance, when seizures are not controlled despite an adequate prescription
(6) When a patient receiving an antiepileptic drug exhibiting zero-order kinetics is not controlled, for calculation of the dosage increment
(7) When a particular rate of metabolism is suspected:
(7a) persisting seizures despite large doses of an appropriate drug
(7b) relapse concomitant with hepatic or renal disease
(7c) with prescription of a non-antiepileptic drug
(7d) during pregnancy
(8) In polytherapy
(8a) to monitor drug-to-drug interactions
(8b) when an antiepileptic drug is discontinued
(9) When an abnormal ratio between total and free plasma levels is suspected:
(9a) during pregnancy
(9b) renal failure
(10) When a metabolite is suspected of playing a significant role in the clinical condition.
Endpoint:
(1) Use of serum or plasma levels simply to adjust dosage to keep a drug level within a published "therapeutic" range is not recommended. It may be dangerous to change an effective and well-tolerated regimen simply to get drug levels within a published range.
(2) Each patient should have a target range based on severity of the epilepsy and tolerance to side effects. A patient who is seizure free and does not complain of side effects probably does not need blood level monitoring.
(3) If drug levels are not available or are unreliable, clinical judgment can usually recognize the most common dose-related side effects (drowsiness, dizziness, gastrointestinal disturbances, etc.).
Some factors affecting drug levels:
(1) compliance
(2) formulation of medication
(3) change in absorption, due to food interactions or gastrointestinal disease
(4) change in body weight
(5) changes in volume of distribution, with advancing age or pregnancy
(6) change in binding to plasma proteins, affecting free drug levels
(7) change in drug metabolism, especially related to drug interactions or end-organ disease
(8) change in drug excretion, including effect of altered urinary pH
Specialty: Toxicology, Emergency Medicine, Critical Care, Neurology
